Andrew J Synn1,2, Chunyi Zhang1, George R Washko3,4, Raúl San José Estépar5, George T O'Connor4,6, Wenyuan Li7, Murray A Mittleman7, Mary B Rice1. 1. 1 Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center. 2. 2 Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital. 3. 3 Division of Pulmonary and Critical Care Medicine, and. 4. 4 U.S. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts. 5. 5 Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 6. 6 Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts; and. 7. 7 Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
Abstract
Rationale: Cigarette smoke exposure is a risk factor for many lung diseases, and histologic studies suggest that tobacco-related vasoconstriction and vessel loss plays a role in the development of emphysema. However, it remains unclear how tobacco affects the pulmonary vasculature in general populations with a typical range of tobacco exposure, and whether these changes are detectable by radiographic methods. Objectives: To determine whether tobacco exposure in a generally healthy population manifests as lower pulmonary blood vessel volumes and vascular pruning on imaging. Methods: A total of 2,410 Framingham Heart Study participants with demographic data and smoking history underwent volumetric whole-lung computed tomography from 2008 to 2011. Automated algorithms calculated the total blood volume of all intrapulmonary vessels (TBV), smaller peripheral vessels (defined as cross-sectional area <5 mm2 [BV5]), and the relative fraction of small vessels (BV5/TBV). Tobacco exposure was assessed as smoking status, cumulative pack-years, and second-hand exposure. We constructed multivariable linear regression models to evaluate associations of cigarette exposure and pulmonary blood vessel volume measures, adjusting for demographic covariates, including age, sex, height, weight, education, occupation, and median neighborhood income. Results: All metrics of tobacco exposure (including smoking status, pack-years, and second-hand exposure) were consistently associated with higher absolute pulmonary blood vessel volume, higher small vessel volume, and/or higher small vessel fraction. For example, ever-smokers had a 4.6 ml higher TBV (95% confidence interval [CI] = 2.9-6.3, P < 0.001), 2.1 ml higher BV5 (95% CI = 1.3-2.9, P < 0.001), and 0.28 percentage-point-higher BV5/TBV (95% CI = 0.03-0.52, P = 0.03) compared with never-smokers. These associations remained significant after adjustment for percent predicted forced expiratory volume in 1 second, cardiovascular comorbidities, and did not differ based on presence or absence of airflow obstruction. Conclusions: Using computed tomographic imaging, we found that cigarette exposure was associated with higher pulmonary blood vessel volumes, especially in the smaller peripheral vessels. Although, histologically, tobacco-related vasculopathy is characterized by vessel narrowing and loss, our results suggest that radiographic vascular pruning may not be a surrogate of these pathologic changes.
Rationale: Cigarette smoke exposure is a risk factor for many lung diseases, and histologic studies suggest that tobacco-related vasoconstriction and vessel loss plays a role in the development of emphysema. However, it remains unclear how tobacco affects the pulmonary vasculature in general populations with a typical range of tobacco exposure, and whether these changes are detectable by radiographic methods. Objectives: To determine whether tobacco exposure in a generally healthy population manifests as lower pulmonary blood vessel volumes and vascular pruning on imaging. Methods: A total of 2,410 Framingham Heart Study participants with demographic data and smoking history underwent volumetric whole-lung computed tomography from 2008 to 2011. Automated algorithms calculated the total blood volume of all intrapulmonary vessels (TBV), smaller peripheral vessels (defined as cross-sectional area <5 mm2 [BV5]), and the relative fraction of small vessels (BV5/TBV). Tobacco exposure was assessed as smoking status, cumulative pack-years, and second-hand exposure. We constructed multivariable linear regression models to evaluate associations of cigarette exposure and pulmonary blood vessel volume measures, adjusting for demographic covariates, including age, sex, height, weight, education, occupation, and median neighborhood income. Results: All metrics of tobacco exposure (including smoking status, pack-years, and second-hand exposure) were consistently associated with higher absolute pulmonary blood vessel volume, higher small vessel volume, and/or higher small vessel fraction. For example, ever-smokers had a 4.6 ml higher TBV (95% confidence interval [CI] = 2.9-6.3, P < 0.001), 2.1 ml higher BV5 (95% CI = 1.3-2.9, P < 0.001), and 0.28 percentage-point-higher BV5/TBV (95% CI = 0.03-0.52, P = 0.03) compared with never-smokers. These associations remained significant after adjustment for percent predicted forced expiratory volume in 1 second, cardiovascular comorbidities, and did not differ based on presence or absence of airflow obstruction. Conclusions: Using computed tomographic imaging, we found that cigarette exposure was associated with higher pulmonary blood vessel volumes, especially in the smaller peripheral vessels. Although, histologically, tobacco-related vasculopathy is characterized by vessel narrowing and loss, our results suggest that radiographic vascular pruning may not be a surrogate of these pathologic changes.
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